T lymphocyte growth depends upon the polypeptide growth factor interleukin 2 (IL-2) which specifically binds to a glycoprotein receptor. The receptor for IL-2 has been shown to bind its ligand with high and low affinity. The molecular properties that distinguish the high and low affinity IL-2 receptors are unknown, although an undefined tissue-specific mechanism is involved. The propose experiments will exploit our anti-IL-2 receptor antibodies and our expressible cDNA to the murine IL-2 receptors to attempt to provide a molecular definition of the high and low affinity IL-2 receptors. Ligand-receptors binding studies will be performed on viable cells that contain high affinity IL-2 receptors or on membranes, detergent solubilized membranes, or secreted receptors from the same cells. The mouse IL-2 receptor cDNA will be molecularly engineered to produce the secreted IL-2 receptors. These binding studies will evaluate the extent that the IL-2 receptor microenvironment controls IL-2 binding affinity and examine whether high affinity binding is controlled at multiple levels. The biochemical properties that may distinguish these two forms of the IL-2 receptor will be studied by comparison of the structures of purified high and low affinity IL-2 receptors. These studies will be complemented by chemical crosslinking analysis of the membrane molecules that may associate with the IL-2 receptor and by evaluating the potential relevance of such receptor associated molecules information of a functional IL-2 receptors complex. Tranfection studies using the full-length IL-2 receptor cDNA will be performed with various murine and human lymphoid tumor cell populations. These studies will determine the tendency of various cells to express the tissue-specific properties leading to cell surface expression of high affinity IL-2 receptors and will permit an assessment of whether the IL-2 receptor functions in cells that do not normally express this protein or whether cellular activation of these cells leads to an alteration of biological function of the IL-2 receptors. Since the available data suggest that only IL-2 receptors that bind IL-2 with a high affinity are capable of generating a biological signal, molecular definition of these receptors is directly relevant to understanding the basic of T lymphocyte clonal expansion. Since IL-2 has been implicated in various T and B cell responses, these studies are also relevant to the basis by which an immune response may be regulated.